CNS relapse in DLBCL patients below 60 years treated with R-ACVBP, R-CHOEP, or R-CHOP: A joint analysis of LYSA and GLA/DSHNHL.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7543-7543
Author(s):  
Catherine Thieblemont ◽  
Bettina Altmann ◽  
Olivier Casasnovas ◽  
Fabian Frontzek ◽  
Franck Morschhauser ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Risk Groups ◽  
Observation Time ◽  
Joint Analysis ◽  
High Dose ◽  
First Line Therapy ◽  
Cns Relapse ◽  
Prophylactic Measures ◽  
Multicenter Clinical Trials

7543 Background: Central nervous system (CNS) relapse occurs in 2-6% of DLBCL patients (pts) increasing to 10% or more in high-risk groups. Intrathecal (IT) or intravenous high-dose methotrexate (HD MTX) have limited if any prophylactic impact on CNS relapse. To address the role of systemic first-line therapy in pts tolerating intensified strategies (R-ACVBP, R-(Mega)CHOEP, R-CHO(E)P), we compared CNS relapses occurring in a large cohort of pts ≤60 years. Methods: We conducted a retrospective analysis including previously untreated pts with DLBCL by central review, age 18-60 years, from multicenter clinical trials conducted by LYSA and GLA/DSHNHL (Table). We assessed the risk of CNS relapse in matched cohorts based on the aaIPI. Results: A total of 2203 pts were included. Median age was 47 years (18-60). 455 pts were treated with R-ACVBP, 444 with R-(Mega)CHOEP, 1304 with R-CHOP. Distribution of CNS IPI was not significantly different comparing R-ACVBP to R-CHO(E)P groups within aaIPI categories (Table). PFS and OS were comparable according to treatment within aaIPI groups, also adjusted for prognostic factors. No CNS events occured during observation time of 3 years in pts with aaIPI 0. In pts with aaIPI 1, no CNS event occured in the R-ACVPB arm, the 3y-cumulative incidence of CNS relapse for pts treated with R-CHO(E)P group was 1.0% (95%CI 0.3-1.7). In pts with aaIPI 2,3 and intermediate/high CNS IPI, four (1.6%) treated with R-ACVBP experienced relapse in the CNS compared to 15 (3.9%) pts treated with R-(Mega)CHO(E)P (3y-cumulative incidence 1.6% (95%CI 0-3.2) vs. 4.0% (95%CI 2.0-6.0). Conclusions: CNS relapse was extremely rare in younger DLBCL pts with aaIPI 0 or 1; prophylactic measures are not warranted. In pts with aaIPI 2,3 (and intermediate/high CNS-IPI), only 4 (1.6%) CNS relapses were seen with the R-ACVBP while 15 (3.9%) relapses did occur after R-(Mega)CHO(E)P. This analysis underlines the important role of the systemic therapy in controling CNS relapse.[Table: see text]

Reversal of Resistance to Doxifluridine and Fluorouracil in Metastatic Colorectal Cancer: The Role of High-Dose Folinic Acid

1992 ◽  
Vol 78 (4) ◽  
pp. 258-261 ◽  
Author(s):  
Marco Colleoni ◽  
Emilio Bajetta ◽  
Filippo de Braud ◽  
Nicoletta Zilembo ◽  
Franco Noiè ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
First Line ◽  
First Line Therapy ◽  
Colon And Rectum

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) dally for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridlne, a new fluoropyrimldine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64 %), lung (35 %), local recurrence (10 %) and peritoneum (10 %). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxlfluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.

Impact of metformin on outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 531-531
Author(s):  
Lana Hamieh ◽  
Rana R. McKay ◽  
Suzanne S Mickey ◽  
Xun Lin ◽  
Ronit Simantov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cox Regression ◽  
Mapk Pathway ◽  
Risk Groups ◽  
Diabetic Patients ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Tumor Types ◽  
Phase Ii And Iii

531 Background: Metformin has been shown to confer anti-neoplastic properties in several tumor types. Its effect on outcomes in mRCC patients has not been completely characterized. In this study, we evaluated the role of metformin on survival outcomes in pts with mRCC. Methods: We conducted a retrospective study of pts with mRCC treated on several phase II and III clinical trials from 2003-2013. We analyzed overall survival (OS) in the metformin users versus non-users using the Cox regression model and the Kaplan-Meier method. Results: We identified 4,736 pts with mRCC including 486 diabetic pts of whom 218 (4.6%) were metformin users. The majority were <65 years of age (69%), male (71%), with clear-cell histology (89%) and prior nephrectomy (70%). With regard to IMDC risk groups, 14%, 42%, and 24% had favorable, intermediate, and poor-risk disease, respectively. Pts received treatment with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (TEM) (n=457), TEM + interferon (IFN)-α (n=208), bevacizumab (BEV) + TEM (n=393), BEV + IFN-α (n=391), or IFN-α (n=560); overall 3,044 (64%) received first-line therapy. In the total cohort, metformin use did not impact OS when compared to users of other anti-diabetic agents (p=0.17) or non-diabetics (p=0.69). In diabetic pts, metformin use did not confer a survival advantage when stratified by type of therapy and IMDC risk group. However, in the cohort of diabetic pts receiving sunitinib (n=128), metformin use was associated with an improvement in OS when compared to users of non-metformin anti-diabetic agents (29.3 versus 20.9 months, respectively, p=0.0008, HR 0.051, 95% CI 0.009, 0.292). Conclusions: This is the largest study to date investigating the role of metformin on outcomes in mRCC pts. In this analysis, we demonstrate that concomitant use of metformin may improve survival in diabetic pts with mRCC treated with sunitinib. Based on preclinical data, we hypothesize that the mechanism underlying this survival benefit may be related to synergistic inhibition of the MAPK pathway. However, the study is limited by the small number of diabetic patients. Larger prospective studies are warranted to validate these results.

scholarly journals Incidence of Adult-Onset Epilepsy and the Contributory Role of Neurocysticercosis in a Five-Year, Population-Based, Prospective Study in Rural Ecuador

2021 ◽  
Author(s):  
Oscar H. Del Brutto ◽  
Bettsy Y. Recalde ◽  
Robertino M. Mera
Keyword(s):  
Cumulative Incidence ◽  
Alcohol Intake ◽  
Population Based ◽  
Observation Time ◽  
Adult Onset ◽  
High Incidence ◽  
Incident Rate ◽  
Relevant Covariates

This prospective cohort study aimed to assess incidence and etiology of adult-onset epilepsy in previously seizure-free Atahualpa residents aged ≥ 20 years. Persons with adult-onset epilepsy occurring over 5 years were identified from annual door-to-door surveys and other overlapping sources. Those who emigrated or declined consent were excluded at the administrative censoring date of the last survey when these subjects were interviewed. Persons who died and those who developed incident epilepsy were censored at the time of these outcomes. Poisson regression models adjusted for demographics, education, alcohol intake, and the length of observation time, were used to estimate annual adult-onset epilepsy incidence rate ratio and cumulative incidence. Systematic neuroimaging screening was offered to participants to get insights on the etiology of epilepsy. Individuals enrolled in this cohort (N = 1,480) contributed to 6,811.6 years of follow-up. Seventeen developed incident adult-onset epilepsy, for an annual incident rate of 249.2 per 100,000 persons-year (95% CI: 130.7–367.7). Cumulative incidence was 1,245.9 per 100,000 persons (95% CI: 653.7–1,838.3) after a mean of 4.6 (SE: 0.06) years of follow-up. Six persons with incident epilepsy had neurocysticercosis (35%). Individuals with neurocysticercosis were six times more likely to develop adult-onset epilepsy than those without this disease (IRR: 6.01; 95% CI: 2.16–16.7), after adjusting for relevant covariates. The attributable fraction of incident adult-onset epilepsy due to neurocysticercosis was 30.9% (95% CI: 25.6–46.2%). This rural Ecuadorian population has a high incidence of adult-onset epilepsy, with neurocysticercosis being an important contributory cause.

scholarly journals Real-World Data (RWD) on the 3-Year Follow-Up Outcomes of Different CNS Prophylaxis Strategies Across CNS-IPI Risk Groups in Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

2021 ◽  
pp. 486-494
Author(s):  
Anadil Faqah ◽  
Summaiya Asif ◽  
Suleyman Yasin Goksu ◽  
Hassan S. Sheikh
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Relapse Rate ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
High Dose ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Large B Cell ◽  
Prophylaxis Strategy

PURPOSE CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis with a median survival of about 2.5 months. Data demonstrating best prophylactic strategy remain controversial and need further definition. PATIENTS AND METHODS We present data of 110 patients with DLBCL treated with standard systemic therapy divided into four groups based on primary CNS prophylaxis strategy and CNS International Prognostic Index (IPI) risk categories. We compared their 3-year CNS relapse rate and overall survival in each group. RESULTS The CNS prophylaxis strategy consisted of intrathecal (IT) methotrexate (MTX) in group 1, high-dose (HD) MTX in group 2, combination IT and HD MTX in group 3, and IT and/or HD MTX with intensive chemotherapy in group 4. At 3 years, CNS relapse rate was 8.6% (4/46), 8.3% (1/12), 4.8% (2/42), and 18% (2/11) in groups 1-4 ( P = .64), respectively. According to CNS IPI, the CNS relapse rate was 16.6%, 10.1%, and 0% in high-, intermediate-, and low-risk groups, respectively. The 3-year overall survival rate was 69%, 75%, 80%, and 45% in groups 1-4 ( P = .71), respectively. CONCLUSION Our study while did not find statistical significance did indicate a lower incidence of CNS relapse with the addition of systemic HD MTX to IT MTX in the high-risk DLBCL population.

Impact of Chromosome 13 Deletion and Plasma Cell Load on Long-Term Survival of Patients with Multiple Myeloma Undergoing Autologous Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5148-5148
Author(s):  
Esbjörn Paul ◽  
Tolga Sutlu ◽  
Evren Alici ◽  
Goesta Gahrton ◽  
Hareth Nahi
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Autologous Transplantation ◽  
High Dose ◽  
Prognostic Impact ◽  
Term Survival ◽  
Chromosome 13 ◽  
First Line Therapy

Abstract High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common treatment for patients under 60–65 years of age with multiple myeloma (MM). In this study, we present a retrospective analysis of the prognostic impact of different factors in patients who have received this treatment as first line therapy in our centre. Abnormalities in chromosome 13 were identified by fluorescence in situ hybridization at the time of diagnosis. The median OS and PFS from transplantation time in the whole group of 193 patients were 90 and 48 months respectively. The median follow-up was 65 months (range: 6–186 months). The complete remission (CR) rate in patients with and without del(13) was 31% and 40% respectively whereas the median OS in patients with del(13) was 58 months but not reached in patients without del(13) (p=0.006). The PFS was 26 months in patients with del(13) and 84 months in those without del(13) (p=0.001). The transplantation related mortality was 2.5% both in the absence and presence of del(13). Patients who achieved CR following ASCT had longer OS and PFS when compared to those who only achieved partial remission. Thus, this study confirms the role of del(13) as a marker of poor prognosis. Multivariate analysis showed that the existence of del(13) was the only single independent factor effecting survival (p=0.001). In patients without del(13), the prognostic impact was even stronger when combined with the plasma cell load in the bone marrow (p=0.020), whereas the plasma cell load had no effect on survival of patients with del(13). Overall, the absence of del(13) in combination with low plasma cell infiltration at diagnosis predicts the best survival.

High Prevalence of FLT3 - ITD Mutations in Patients (pts) with Acute Myeloid Leukemia (AML) Who Present with Central Nervous System (CNS) Relapse.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1020-1020 ◽  
Author(s):  
Fabio P S Santos ◽  
Hagop Kantarjian ◽  
Tapan Kadia ◽  
Carol Bivins ◽  
Susan Obrien ◽  
...  
Keyword(s):  
Brain Mri ◽  
Cranial Nerves ◽  
High Dose ◽  
Mutation Status ◽  
Cns Disease ◽  
Flt3 Mutation ◽  
Cns Relapse ◽  
Prophylactic Measures ◽  
High Prevalence ◽  
Active Disease

Abstract Abstract 1020 Poster Board I-42 Despite achievement of complete remission (CR) rates of 70% with modern chemotherapeutic regimens, most pts with AML eventually relapse. CNS extramedullary relapses have become uncommon with the use of high-dose cytarabine (HDAC; > 1.0 g/m2) containing regimens. The clinical and molecular features associated with a higher risk of CNS relapse are not defined. We analyzed adults who presented with AML and CNS relapses from 2005 until 2009. CNS leukemia was diagnosed by the presence of leukemic blasts in a cytocentrifuge preparation of cerebrospinal fluid (CSF). Patients with blasts in the CSF together with high numbers of red blood cells (> 5) were not considered to have CNS disease if the blasts were high in the peripheral blood ( 5 × 109/L). All pts with evidence of CNS disease underwent a marrow examination. There were 10 pts with a diagnosis of AML and CNS relapse observed during the above mentioned time period. Median age was 38 years (range 23-56) and 80% were female. At time of first diagnosis the median WBC was 61×109/L and 50% had M4/M5 phenotype by FAB. Six pts had received induction chemotherapy containing standard doses of cytarabine; five of them received HDAC as consolidation courses afterwards. Four pts received induction regimens containing HDAC. The CR rate was 80% (8 of 10 pts). The median CR duration was 6 months (range 3-7). CNS involvement was detected at a median of 8 months after diagnosis (range 5-29). No pt had isolated CNS relapse. CNS disease was detected in the setting of refractory AML (N=2), 1st systemic relapse (N=4) or 2nd and subsequent relapses (N=4). Eight pts had neurologic symptoms at time of CNS relapse, including headache (N=3), involvement of cranial nerves (N=2), visual impairment (N=1), seizures (N=1), confusion (N=1) and feet neuropathy (N=1) (one pt had more than one symptom). CNS imaging was done in 8 pts, and three pts had abnormal findings by MRI suggestive of CNS disease. The median cell count on CSF was 305 (range 0-880) and median blast percentage was 89%. Two pts had zero cells with blasts detected on cytocentrifuge preparation only. None of the 2 pts had circulating blasts and both had abnormal findings on brain MRI suggestive of CNS relapse. Cytogenetic information was available at initial diagnosis for 9 pts, being diploid in 6 pts. The pt without cytogenetic information was diploid at time of relapse. FLT3 mutation status was unknown at time of diagnosis in six pts, being positive for the ITD mutation in 4 pts. At time of 1st relapse, FLT3 mutation status was positive in 8 pts (80%; all cases were FLT3-ITD). Treatment for CNS disease consisted of intrathecal chemotherapy (methotrexate alternating with cytarabine) in all pts and whole brain radiation therapy in one (24 Gy in 12 fractions). Therapy was successful in clearing all signs of CNS disease in 9 pts. One pt persisted with disease after 4 intrathecal injections and expired 6 weeks afterwards. Five pts had additional CNS relapses at a median of 3 months (range 2-15) after being first diagnosed with CNS disease. Stem cell transplantation (SCT) was done in 3 pts, 2 with active disease and one in CR. All three relapsed with CNS disease after SCT. Only one pat currently remains alive and with active disease. Median survival after CNS relapse was 3 months (range 1-28). In conclusion, CNS relapse is a rare occurrence in AML and is associated with a poor prognosis. A high prevalence of FLT3-ITD mutations was observed in these pts; FLT3 mutations are associated with elevated WBC counts, which are traditionally considered a risk factor for CNS relapse. Analysis of merged data from larger databases may help to better discern the association between FLT3-ITD mutations and CNS relapse. If confirmed, prophylactic measures might be considered for such pts. Disclosures: Jabbour: Novartis: Speakers Bureau; Bristol Myers Squibb : Speakers Bureau.

Incidence of Central Nervous System (CNS) Relapse in De Novo Adult Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 940-940
Author(s):  
Deborah A. Thomas ◽  
Susan O'Brien ◽  
Michael Rytting ◽  
Farhad Ravandi ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Systemic Chemotherapy ◽  
De Novo ◽  
Risk Groups ◽  
High Dose ◽  
Proliferative Index ◽  
Cns Disease ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Relapse Rates

Abstract In the era of improved outcomes with systemic chemotherapy for de novo adult ALL, prevention of CNS relapse becomes even more paramount. Isolated CNS relapse may herald eventual marrow relapse in the absence of definitive CNS-directed and systemic chemotherapy strategies. CNS prophylaxis can be successfully achieved with intrathecal chemotherapy treatments (IT) in conjunction with systemic chemotherapy inclusive of high-dose methotrexate (MTX) and/or high-dose cytarabine (ara-C) without use of radiation therapy (XRT). The hyper-CVAD regimen (cycles of fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with cycles of high dose MTX (1 g/m2) and cytarabine (3 gm/m2; 1 gm/m2 for age > 60 yrs) incorporates IT MTX alternating with IT ara-C during the intensive phase of induction-consolidation. The number of IT treatments was determined by CNS risk (4 IT for low risk = LDH < 1400 U/L and low proliferative index; 16 IT for high risk = LDH > 1400 U/L or high proliferative index; 8 IT for indeterminate risk = one of parameters unknown). An analysis performed in 2000 (Kantarjian et al, J Clin Oncol 18: 547, 2000) identified CNS relapse rates of 6%, 2%, and 0% for the low, high, and indeterminate CNS risk groups, respectively. The number of IT administered was modified from 4 to 6, from 16 to 8, and maintained at 8 for these CNS risk groups, respectively, until 2010, at which point all pts received 8 IT. An analysis was conducted to examine the incidence of CNS relapse for 565 pts with de novo ALL treated with hyper-CVAD-based regimens (n=453, inclusive of nelarabine, monoclonal antibodies such as rituximab, ofatumumab or inotuzumab, and/or tyrosine kinase inhibitors such as imatinib, dasatinib or ponatinib) from 2001 to 2014 or with the augmented BFM regimen (one IT ara-C, 15 IT MTX, Capizzi methotrexate) (n=112) from 2006 to 2014. T-lymphoblastic lymphoma (designated for 8 IT) and Burkitt leukemia/lymphoma (designated for 16 IT) cases were excluded from the analysis. The incidence of CNS relapse (n=42) was 7% overall; 59% were isolated CNS relapses (n=25, 5%) without concurrent marrow relapse. Median time to isolated CNS relapse was 19 mos versus 10 mos for concurrent relapse. The incidence of CNS relapse for cases with CNS disease at initial presentation (n=70) was 19%. Factors predictive of higher incidence of CNS relapse included younger age (12% for 30 yrs or younger, 3.5% for 60 yrs or older, p=.01), elevated LDH > 1400 U/L (13% vs 4%, p<.001), and Philadelphia chromosome positivity (12% vs 6%, p=.05). The overall CNS relapse rates were 4% for the hyper-CVAD and monoclonal antibody regimens; 11% for the augmented BFM regimen, and 14%-15% for the hyper-CVAD and imatinib/dasatinib regimens. The CNS relapse rate declined from 10% for pts treated prior to 2010 to 8% thereafter (8 IT for all risk groups). Overall, the 3-yr survival rates for CNS relapse was 47% vs 63% without CNS relapse (p=0.006). Modifications to the hyper-CVAD and tyrosine kinase inhibitor regimens for Philadelphia positive ALL have been implemented to increase the number of IT from 8 to 12. Similar modifications will be implemented for the augmented BFM regimen with consideration for incorporation of high dose MTX. Additional analyses will further refine the CNS risk model in order to guide CNS prophylaxis. Alternative agents such as IT rituximab may improve outcomes for CD20 positive cases with CNS disease at presentation; a clinical trial in the setting of active CNS disease is underway. Disclosures No relevant conflicts of interest to declare.

scholarly journals High dose methotrexate in the treatment of children with acute lymphoblastic leukemia

2007 ◽  
Vol 47 (1) ◽  
pp. 1 ◽  
Author(s):  
Johannes Bondan Lukito
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Risk Groups ◽  
Observation Time ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Minor Disease ◽  
State Concentration

Background It has been claimed that around 70% of childhoodacute lymphoblastic leukemia (ALL) can be cured. One of theimportant role is high dose methotrexate (HDMTX) administrationduring the consolidation therapy.Objective To determine the safety and effectiveness of HDMTXin children with ALL.Methods We reviewed patients with ALL in Pantai Indah KapukHospital, Jakarta during the period August 2000 through July 2005with observation time run through September 2006. Only patientswith normal kidney function were allowed to have HDMTX. Besidesgood hydration and alkalinization, patients were supported with goodhygiene (mouth, skin and anal area). MTX was given in loadingdose of 10% from the total dose in ½ hour and the rest 23½ hours for90%. Leucovorin rescue was started 12 hours after discontinuationof 24 hour MTX IV infusion. Leucovorin was given until the MTXconcentration reached 0.1 uM/L. Patients were stratified to low,intermediate and high risk groups; 2 gram/m 2 was given to low riskgroup and 5 gram/m2 to intermediate and high risk groups.Results There were 20 patients eligible for study. All methotrexatesteady-state plasma concentrations (MTX Cp ss ) were above 16 uM/L, and steady state concentration in CSF was always below 0.5 uM/L for 2 gram/m 2 and above 0.5 uM/L for 5 gram/m 2 doses. All 20cases went through the procedure with only mild side effects i. e,mild mucositis, anal furuncle and diarrhea, which recovered 2 weekslater. Only 1 high risk case with initial WBC 612X10 9 /L, succumbedafter he went through the HDMTX program smoothly and relapsedsubsequently during reinduction phase.Conclusion HDMTX can be given safely to ALL patients with normalkidney function with good supportive care. Five gram/m 2 HDMTXeffectively treat the minor disease and/or prevent CNS and testicularleukemia. This study has also given an impression that HDMTXmay increase event-free survival.

Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1078-1084 ◽  
Author(s):  
Lionel Adès ◽  
Miguel A. Sanz ◽  
Sylvie Chevret ◽  
Pau Montesinos ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cumulative Dose ◽  
Promyelocytic Leukemia ◽  
Joint Analysis ◽  
High Dose ◽  
Newly Diagnosed ◽  
All Trans Retinoic Acid ◽  
High Cumulative Dose ◽  
Wbc Count

Abstract All-trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed. We performed a joint analysis of patients younger than 65 years included in Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA) LPA 99 trial, where patients received no AraC in addition to ATRA, high cumulative dose idarubicin, and mitoxantrone, and APL 2000 trial, where patients received AraC in addition to ATRA and lower cumulative dose daunorubicin. In patients with white blood cell (WBC) count less than 10 × 109/L, complete remission (CR) rates were similar, but 3-year cumulative incidence of relapse (CIR) was significantly lower in LPA 99 trial: 4.2% versus 14.3% (P = .03), although 3-year survival was similar in both trials. This suggested that AraC is not required in APL with WBC count less than 10 × 109/L, at least in trials with high-dose anthracycline and maintenance treatment. In patients with WBC of 10 × 109/L or more, however, the CR rate (95.1% vs 83.6% P = .018) and 3-year survival (91.5% vs 80.8%, P = .026) were significantly higher in APL 2000 trial, and there was a trend for lower 3-year CIR (9.9% vs 18.5%, P = .12), suggesting a beneficial role for AraC in those patients.

scholarly journals A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial

Blood ◽  
2020 ◽  
Vol 136 (16) ◽  
pp. 1813-1823 ◽  
Author(s):  
Daisuke Tomizawa ◽  
Takako Miyamura ◽  
Toshihiko Imamura ◽  
Tomoyuki Watanabe ◽  
Akiko Moriya Saito ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
University Hospital ◽  
High Dose ◽  
Pediatric Leukemia ◽  
Hematopoietic Stem

Abstract The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children’s Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n = 15), IR (n = 19), or HR (n = 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ≥0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.

Sign in / Sign up

Export Citation Format

Share Document